Osteoporosis is a disease characterized by a deficiency of bone that affects both the protein matrix and the mineral fraction, resulting in a decrease in the resistance of bones to fracture. Osteoporosis is generally diagnosed by means of dual energy x-ray absorptiometry (DEXA), which provides a quantitative measurement of the amount of mineral present in bone and allows determination of fracture risk at a measured site. A decrease in bone mineral density (BMD) as measured by DEXA is indicative of osteoporosis and increased risk of fractures. See, for example, Nevitt and Cummings (1993) J. Am. Geriatr. Soc. 41:1226; and Parfitt (1993) Calcif. Tissue Int. 53:S82.
While bone densitometry is the current gold standard for diagnosis of bone diseases such as osteoporosis, this method is limited to measuring bone mass, and it does not take into consideration the microarchitecture of the bone, the crystal organization, size and shape, the connectivity of the trabecullar network, and the structure of the bone proteins. Further, the lack of perfect correlation between bone mineral density and bone fractures suggests that low bone mineral density is not the only cause of fragile bones (Ott (1993) Calcif. Tissue Int. 53(Suppl.):S7). Thus, while the degree of mineralization is the current standard by which osteoporosis is diagnosed, it is unable to detect bone fragility due to deficiency in protein matrix.
Moreover, DEXA is a relatively expensive diagnostic procedure that exposes the patient to potentially harmful x-rays; thus it cannot be used for mass screenings, such as at routine checkups. Therefore, it is possible that clinicians will under diagnose patients at risk for fracture because the bone disease is often unrecognized until a fracture occurs, or because bone mineral density does not always correlate with a risk of fragile bones even when DEXA is used. The alternative of obtaining collagen from a patient's bones is an even more expensive and risky procedure. Thus, clinicians need new, low-risk methods to diagnose patients that are at an increased risk of bone fracture.